Weaponizing chitosan and its derivatives in the battle against lung cancer.

Lung cancer (LC) is a crisis of catastrophic proportions. It is a global problem and urgently requires a solution. The classic chemo drugs are lagging behind as they lack selectivity, where their side effects are spilled all over the body, and these adverse effects would be terribly tragic for LC patients. Therefore, they could make a bad situation worse, inflict damage on normal cells, and inflict pain on patients. Since our confidence in classic drugs is eroding, chitosan can offer a major leap forward in LC therapy. It can provide the backbone and the vehicle that enable chemo drugs to penetrate the hard shell of LC. It could be functionalized in a variety of ways to deliver a deadly payload of toxins to kill the bad guys. It is implemented in formulation of polymeric NPs, lipidic NPs, nanocomposites, multiwalled carbon nanotubes, and phototherapeutic agents. This review is a pretty clear proof of chitosan's utility as a weapon in battling LC. Chitosan-based formulations could work effectively to kill LC cells. If a researcher is looking for a vehicle for medication for LC therapy, chitosan can be an appropriate choice.

The promising antioxidant effects of lignans: Nrf2 activation comes into view.

Lignans are biologically active compounds widely distributed, recognized, and identified in seeds, fruits, and vegetables. Lignans have several intriguing bioactivities, including anti-inflammatory, antioxidant, and anticancer activities. Nrf2 controls the expression of many cytoprotective genes. Activation of Nrf2 is a promising therapeutic approach for treating and preventing diseases resulting from oxidative injury and inflammation. Lignans have been demonstrated to stimulate Nrf2 signaling in a variety of in vitro and experimental animal models. The review summarizes the findings of fourteen lignans (Schisandrin A, Schisandrin B, Schisandrian C, Magnolol, Honokiol, Sesamin, Sesamol, Sauchinone, Pinoresinol, Phyllanthin, Nectandrin B, Isoeucommin A, Arctigenin, Lariciresinol) as antioxidative and anti-inflammatory agents, affirming how Nrf2 activation affects their pharmacological effects. Therefore, lignans may offer therapeutic candidates for the treatment and prevention of various diseases and may contribute to the development of effective Nrf2 modulators.

Role of immunotherapies and stem cell therapy in the management of liver cancer: A comprehensive review.

Liver cancer (LC) is the sixth most common disease and the third most common cause of cancer-related mortality. The WHO predicts that more than 1 million deaths will occur from LC by 2030. Hepatocellular carcinoma (HCC) is a common form of primary LC. Today, the management of LC involves multiple disciplines, and multimodal therapy is typically selected on an individual basis, considering the intricate interactions between the patient's overall health, the stage of the tumor, and the degree of underlying liver disease. Currently, the treatment of cancers, including LC, has undergone a paradigm shift in the last ten years because of immuno-oncology. To treat HCC, immune therapy approaches have been developed to enhance or cause the body's natural immune response to specifically target tumor cells. In this context, immune checkpoint pathway inhibitors, engineered cytokines, adoptive cell therapy, immune cells modified with chimeric antigen receptors, and therapeutic cancer vaccines have advanced to clinical trials and offered new hope to cancer patients. The outcomes of these treatments are encouraging. Additionally, treatment using stem cells is a new approach for restoring deteriorated tissues because of their strong differentiation potential and capacity to release cytokines that encourage cell division and the formation of blood vessels. Although there is no proof that stem cell therapy works for many types of cancer, preclinical research on stem cells has shown promise in treating HCC. This review provides a recent update regarding the impact of immunotherapy and stem cells in HCC and promising outcomes.

An optimized design for motivated broadband LPDA antenna.

This paper presents a super wideband and high-gain log periodic dipole array (LPDA) antenna. The overall structure of the antenna was constructed using microwave studio computer simulation technology. The optimal sizes of the planned antenna are 39 × 10× 0.254 mm3. The engineered antenna arrangement is implemented on an RT5880 substrate as a dielectric medium. The LPDA is arranged in four arms that are equally spaced on both lines. The main 50Ω feeder line is partially grounded at the back of the substrate. A combination of circular director units is being studied and tuned in a regular pattern at a predefined distance from the antenna. An improvement in gain of 3 dBi is the response of the director units. The Conformist LPDA is adjusted to achieve a wide range of millimeter wave bands ranging from 40 to over 70 GHz. The antenna resonates at 60 GHz, where the maximum realized gain of 14.97 dBi is attained. The antenna was tested for utilization in the V-band involving wireless personal area network (WPAN) applications recommended by IEEE 802.11ad and IEEE 802.15.3c. The outcomes of the constructed antenna elements' tests and simulations agree fairly well. The proposed layout works better than previous efforts in this field.

Inhibition of both NOX and TNF-α exerts substantial renoprotective effects in renal ischemia reperfusion injury rat model.

BACKGROUND AND AIMS: Acute kidney injury (AKI) due to renal ischemia-reperfusion injury (RIRI) is associated with high morbidity and mortality, with no renoprotective drug available. Previous research focused on single drug targets, yet this approach has not reached translational success. Given the complexity of this condition, we aimed to identify a disease module and apply a multitarget network pharmacology approach. METHODS: Identification of a disease module with potential drug targets was performed utilizing Disease Module Detection algorithm using NADPH oxidases (NOXs) as seeds. We then assessed the protective effect of a multitarget network pharmacology targeting the identified module in a rat model of RIRI. Rats were divided into five groups; sham, RIRI, and RIRI treated with setanaxib (NOX inhibitor, 10 mg/kg), etanercept (TNF-α inhibitor, 10 mg/kg), and setanaxib and etanercept (5 mg/kg each). Kidney functions, histopathological changes and oxidative stress markers (MDA and reduced GSH) were assessed. Immunohistochemistry of inflammatory (TNF-α, NF-κB) apoptotic (cCasp-3, Bax/Bcl 2), fibrotic (α-SMA) and proteolysis (MMP-9) markers was performed. RESULTS: Our in-silico analysis yielded a disease module with TNF receptor 1 (TNFR1A) as the closest target to both NOX1 and NOX2. Targeting this module by a low-dose combination of setanaxib, and etanercept, resulted in a synergistic effect and ameliorated ischemic AKI in rats. This was evidenced by improved kidney function and reduced expression of inflammatory, apoptotic, proteolytic and fibrotic markers. CONCLUSIONS: Our findings show that applying a multitarget network pharmacology approach allows synergistic renoprotective effect in ischemic AKI and might pave the way towards translational success.

Comorbidity of depression and type 2 diabetes in Egypt results from the International Prevalence and Treatment of Diabetes and Depression (INTERPRET-DD) study.

BACKGROUND: Diabetes mellitus and depression are serious common diseases, and the number of people with both conditions is rising steadily. Depression in people with diabetes mellitus results in poorer prognosis through different mechanisms. On the other hand, the presence of diabetes in individuals with depression increases functional impairment that is associated with depression. AIMS: The study aimed to assess the prevalence and factors associated with depression among adults with type 2 diabetes mellitus attending a diabetes clinic in Cairo, Egypt. METHODS: A cross-sectional study was conducted among adult patients with diabetes type 2 attending a diabetes clinic in the endocrinology department in Ain Shams University Teaching Hospital, Cairo, Egypt. Data were collected through face-to-face interviews by trained psychiatrists and from patients' records. RESULTS: The prevalence of depression among diabetic patients was 21.8% (95% CI [15.6%, 29.1%]). Depression was more common among younger age groups and those with a higher level of education. There was no significant difference between those with lifetime depression compared to those without depression regarding physical health complications. CONCLUSIONS: The prevalence of depression among patients with type 2 diabetes is high. Given the impact of co-morbid diabetes and depression, diabetic patients should be routinely screened for the latter condition.

Simultaneous Identification of Unroofed Coronary Sinus Atrial Septal Defect and Atrial Septal Defect Secundum Using Cardiac Computed Tomography Angiography.

Unroofed coronary sinus (UCS) represents a rare subtype of atrial septal defect (ASD), an adult congenital heart disease characterized by communication between the systemic and pulmonary circulations at the atrial level. This case report presents the unique occurrence of a large, unrepaired ASD secundum and an incidentally identified UCS type II in a 25-year-old female during a cardiac murmur assessment. The diagnosis of ASD secundum was initially made using transthoracic echocardiography (TTE) and was later confirmed with a transesophageal echocardiogram. The identification of the UCS was achieved through the utilization of cardiac computed tomography angiography (CCTA). Ultimately, the patient underwent a successful reroofing procedure using a bovine pericardial patch.

C3-Spirooxindoles: Divergent chemical synthesis and bioactivities (2018-2023).

This scientific review documents the recent progress of C3-spirooxindoles chemistry (synthesis and reaction mechanism) and their bioactivities, focusing on the promising results as well as highlighting the biological mechanism via the reported molecular docking findings of the most bioactive derivatives. C3-Spirooxindoles are attractive bioactive agents and have been found in a variety of natural compounds, including alkaloids. They are widely investigated in the field of medicinal chemistry and play a key role in medication development, such as antivirals, anticancer agents, antimicrobials, etc. Regarding organic synthesis, several traditional and advanced strategies have been reported, particularly those that started with isatin derivatives.

Stem Cells Reprogramming in Diabetes Mellitus and Diabetic Complications: Recent Advances.

BACKGROUND: The incidence of diabetes mellitus (DM) is dramatically increasing worldwide, and it is expected to affect 700 million cases by 2045. Diabetes influences health care economics, human quality of life, morbidity, and mortality, which were primarily seen extensively in developing countries. Uncontrolled DM, which results in consistent hyperglycemia, may lead to severe life-threatening complications such as nephropathy, retinopathy, neuropathy, and cardiovascular complications. METHODOLOGY: In addition to traditional therapies with insulin and oral anti-diabetics, researchers have developed new approaches for treatment, including stem cell (SC) therapy, which exhibits promising outcomes. Besides its significant role in treating type one DM (T1DM) and type two DM (T2DM), it can also attenuate diabetic complications. Furthermore, the development of insulin-producing cells can be achieved by using the different types of SCs, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and multiple types of adult stem cells, such as pancreatic, hepatic, and mesenchymal stem cells (MSC). All these types have been extensively studied and proved their ability to develop insulin-producing cells, but every type has limitations. CONCLUSION: This review aims to enlighten researchers about recent advances in stem cell research and their potential benefits in DM and diabetic complications.

Baicalin and lung diseases.

Studies focusing on natural products have been conducted worldwide, and the results suggest that their natural ingredients effectively treat a wide range of illnesses. Baicalin (BIA) is a glycoside derived from the flavonoid baicalein present in Scutellaria baicalensis of the Lamiaceae family. Interestingly, BIA has been shown to protect the lungs in several animal models used in numerous studies. Therefore, we fully analyzed the data of the studies that focused on BIA's lung protective function against various injuries and included them in this review. Interestingly, BIA exhibits promising effects against acute lung injury, lung fibrosis, pulmonary embolism, and lung remodelling associated with COPD, LPS, and paraquat insecticide. BAI exhibits anticancer activity against lung cancer. Additionally, BIA potently attenuates lung damage associated with infections. BIA primarily exerts its therapeutic effects by suppressing inflammation, oxidative stress immune response, and apoptosis pathways. Nrf2/HO-1, PI3K/Akt, NF-κB, STAT3, MAPKs, TLR4, and NLRP3 are important targets in the pulmonary therapeutic effects of BIA on different lung disease models. Consequently, we recommend using it in future potential clinical applications, its contribution to treatment guidelines, and translating its promising effects to clinical practice in lung diseases.

Adrenergic receptors blockade alleviates dexamethasone-induced neurotoxicity in adult male Wistar rats: Distinct effects on ß-arrestin2 expression and molecular markers of neural injury.

BACKGROUND: Dexamethasone-induced neurotoxicity has been previously reported. However, the molecular mechanisms are still not completely understood. OBJECTIVES: The current work aimed to investigate the modulatory effects of α- and ß-adrenergic receptors on dexamethasone-induced neurotoxicity in rats focused on changes in ß-arrestin2 and molecular markers of neural injury in cerebral cortex. METHODS: Male Wistar rats were subcutaneously injected with dexamethasone (10 mg/kg/day) for 7 days to induce neural injury in the cerebral cortex. The experiment involved 5 groups: control, dexamethasone, carvedilol, propranolol, and doxazosin. In the last 3 groups, drugs were given 2 hours before dexamethasone injection. At the end of experiment, brain samples were collected for measurement of brain derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), kinase activity of protein kinase B (Akt), diacylglycerol (DAG), α-smooth muscle actin (α-SMA), Smad3, ß-amyloid and phospho-tau protein levels in addition to histopathological examination of brain tissue using hematoxylin-eosin, Nissl, and Sirius red stains. Moreover, ß-arrestin2 levels in the cerebral cortex were measured using immunohistochemical examination. RESULTS: Dexamethasone slightly reduced brain weight and significantly decreased BDNF, Akt kinase activity and ß-arrestin2 but markedly induced degeneration of cortical neurons and significantly increased GFAP, DAG, α-SMA, Smad3, ß-amyloid and phospho-tau protein levels compared to controls. Carvedilol, propranolol, and doxazosin reversed all dexamethasone-induced molecular changes and slightly ameliorated the histopathological changes. Carvedilol significantly increased brain weight and ß-arrestin2 levels compared to dexamethasone, propranolol, and doxazosin groups. CONCLUSION: blocking α- and/or ß-adrenergic receptors alleviate dexamethasone-induced neurotoxicity despite their distinct effects on ß-arrestin2 levels in the cerebral cortex.

Pharmacological update of mirtazapine: a narrative literature review.

Mirtazapine (MTZ) is an antidepressant drug with an exceptional pharmacological profile. It also has an excellent safety and tolerability profile. The present review provides a pharmacological update on MTZ and summarizes the research findings of MTZ's effects on different diseases. MTZ is hypothesized to have antidepressant effects because of the synergy between noradrenergic and serotonergic actions and is effective in treating major depressive disorder and depression associated with epilepsy, Alzheimer's disease, stroke, cardiovascular disease, and respiratory disease. In cancer patients, MTZ significantly reduced sadness, nausea, sleep disruption, and pain and improved quality of life. Also, it has promising effects on Parkinson's disease, schizophrenia, dysthymia, social anxiety disorder, alcohol dependency, posttraumatic stress disorder, panic disorder, pain syndromes, obsessive-compulsive disorder, and sleep disorders. Additionally, MTZ is potentially therapeutic in different situations associated with depression, such as liver, kidney, cardiovascular, respiratory, infertility, heavy metal-induced neurotoxicity, and pruritus. Potent antioxidative, anti-inflammatory, and anti-apoptotic bioactivities mediate these promising effects. These positive outcomes of the scientific investigations motivate more and more clinical trials for a golden exceptional antidepressant in different conditions.

Targeting necroptosis in fibrosis.

Necroptosis, a type of programmed cell death that resembles necrosis, is now known to depend on a different molecular mechanism from apoptosis, according to several recent studies. Many efforts have reported the possible influence of necroptosis in human disorders and concluded the crucial role in the pathophysiology of various diseases, including liver diseases, renal injuries, cancers, and others. Fibrosis is the most common end-stage pathological cascade of several chronic inflammatory disorders. In this review, we explain the impact of necroptosis and fibrosis, for which necroptosis has been demonstrated to be a contributing factor. We also go over the inhibitors of necroptosis and how they have been applied to fibrosis models. This review helps to clarify the role of necroptosis in fibrosis and will encourage clinical efforts to target this pathway of programmed cell death.

Nrf2/HO-1 as a therapeutic target in renal fibrosis.

Chronic kidney disease (CKD) is one of the most prevalent chronic diseases and affects between 10 and 14 % of the world's population. The World Health Organization estimates that by 2040, the disease will be fifth in prevalence. End-stage CKD is characterized by renal fibrosis, which can eventually lead to kidney failure and death. Renal fibrosis develops due to multiple injuries and involves oxidative stress and inflammation. In the human body, nuclear factor erythroid 2-related factor 2 (Nrf2) plays an important role in the expression of antioxidant, anti-inflammatory, and cytoprotective genes, which prevents oxidative stress and inflammation damage. Heme oxygenase (HO-1) is an inducible homolog influenced by heme products and after exposure to cellular stress inducers such as oxidants, inflammatory chemokines/cytokines, and tissue damage as an outcome or downstream of Nrf2 activation. HO-1 is known for its antioxidative properties, which play an important role in regulating oxidative stress. In renal diseases-induced tissue fibrosis and xenobiotics-induced renal fibrosis, Nrf2/HO-1 has been targeted with promising results. This review summarizes these studies and highlights the interesting bioactive compounds that may assist in attenuating renal fibrosis mediated by HO-1 activation. In conclusion, Nrf2/HO-1 signal activation could have a renoprotective effect strategy against CKD caused by oxidative stress, inflammation, and consequent renal fibrosis.

Hepatic ß-arrestins: potential roles in liver health and disease.

Β-arrestins are intracellular scaffolding proteins that have multifaceted roles in different types of disorders. In this review article, we gave a summary about the discovery, characterization and classification of these proteins and their intracellular functions. Moreover, this review article focused on the hepatic expression of ß-arrestins and their hepatocellular distribution and function in each liver cell type. Also, we showed that ß-arrestins are key regulators of distinct types of hepatic disorders. On the other hand, we addressed some important points that have never been studied before regarding the role of ß-arrestins in certain types of hepatic disorders which needs more research efforts to cover.

A meta analysis on the utility of Anakinra in severe COVID-19 disease.

BACKGROUND AND OBJECTIVE: The most important presentation of COVID-19 is hyper inflammatory condition and cytokine storm that occurs due to excessive increase of the inflammatory mediators specially, pro-inflammatory interleukins such as IL-1ß, IL-6 and tumor necrosis factor-α which have an important role in the cytokine storm pathway. Up till now there is not a definitive treatment for COVID-19 disease, but according to the pathophysiology of the disease, Anakinra (Interleukin- 1 inhibitor) is an adjuvant treatment option in patients with severe COVID-19 by blocking the effect of IL-1. So, we aimed to summarize the studies that evaluated the safety and efficacy of Anakinra in patients diagnosed with COVID-19. METHODS: We performed a search in PubMed, Cochrane Library, Scopus, and Web of Science (WOS) databases from inception till 7 Jan 2022. Additionally, we searched randomized and non-randomized clinical trials, cohort, case series, case control, case report more than 3 patients which contain confirmed cases of COVID-19 who received Anakinra (Interleukin- 1 inhibitor) for the management of hyper-inflammatory condition associated with COVID-19 disease. A meta-analysis was conducted using review manager 5.4. RESULTS: We included 44 articles in the systematic review. Ultimately, 23 studies were incorporated in the meta-analysis with a total number of 3179 patients. Our analysis showed statistically significant difference in the following outcomes: duration of ICU stays [MD = -0.65, 95% CI (-1.09, -0.03), p = 0.04], the number of patients who needed invasive mechanical ventilation [RR = 0.57, 95% CI (0.39, 0.84), p = 0.004], and number of deaths [RR = 0.80, 95% CI (0.66, 0.99), p = 0.04]. Our analysis showed no statistically significant difference in the following outcomes: length of hospital stays [MD = -0.16, 95% CI (-0.42, 0.11), p = 0.26], oxygen-free days [MD = -0.81, 95% CI (-3.81, 2.20), p = 0.60], and the number of patients who needed non-invasive mechanical ventilation [RR = 1.09, 95% CI (0.47, 2.52), p = 0.84]. CONCLUSION: Anakinra showed some promising results in important outcomes related to COVID-19 as it significantly reduced the rate of mortality and the need of invasive mechanical ventilation. It should be used in severe cases more than mild and moderate cases to avoid possible immunosuppression complications. Anakinra use is safe in cases of COVID-19 at dose less than 100 mg. Another important outcome was significant reduction is the D-dimer level. Anakinra may be effective in the treatment of specific immunocompromised cases, but it should be used cautiously.

Plasma Homocysteine Levels and Cardiovascular Events in Patients With End-Stage Renal Disease: A Systematic Review.

BACKGROUND: Patients with chronic renal disease or failure are at a heightened risk of mortality due to cardiovascular disease (CVD), which is a predominant cause of death in this population. Hyperhomocysteinemia is prevalent in patients with end-stage renal disease (ESRD), which may increase their susceptibility to CVD. METHODS: We conducted a comprehensive search of PubMed, Science Direct, and Google Scholar for articles published between 2003 and February 2023, using a combination of keywords such as "plasma homocysteine levels," "hyperhomocysteinemia," "end-stage renal disease," "renal failure," "kidney failure," "cardiovascular events," "cardiovascular disease," "myocardial infarction," "coronary artery disease," and "stroke." Our inclusion criteria were studies that investigated the association between total homocysteine (Hcy) level and CVD or total mortality, as well as the impact of vitamin supplementation on cardiovascular or mortality risk. We restricted our search to English-language studies that included ESRD patients and provided data on plasma Hcy levels and associated CVD events. RESULTS: This systematic review includes 11 articles published between 2003 and 2023 that enrolled a total of 3,953 subjects, of whom 79.15% were male patients. All studies included in the review were either quantitative randomized trials or non-randomized studies, such as cross-sectional, cohort, or case-control studies. Of the total studies included, 10 reported either cardiovascular mortality or CVD events, including cardiovascular death, myocardial infarction (MI), angina, and stroke. One study reported the CVD risk score of the patients, and most of them had higher total homocysteine (tHcy) levels. Overall, a total of 817 CVD events were reported across the studies. CONCLUSION: In conclusion, the relationship between Hcy and cardiovascular events in ESRD patients is not straightforward and requires further research. However, our review suggests that Hcy could be a predictor of cardiovascular events in this population, and its nutritional characteristics as well as other associated comorbidities may contribute to its inverse association with outcomes.

The molecular mechanisms underlying anti-inflammatory effects of galangin in different diseases.

When used as an alternative source of drugs to treat inflammation-associated diseases, phytochemicals with anti-inflammatory properties provide beneficial impacts. Galangin is one of the most naturally occurring flavonoids. Galangin has many biological activities, such as anti-inflammatory, antioxidant, antiproliferative, antimicrobial, anti-obesity, antidiabetic, and anti-genotoxic activities. We observed that galangin was well tolerated and positively impacted disease underlying inflammation for the renal, hepatic, central nervous system, cardiovascular, gastrointestinal system, skin, and respiratory disorders, as well as ulcerative colitis, acute pancreatitis, retinopathy, osteoarthritis, osteoporosis, and rheumatoid arthritis. Galangin anti-inflammatory effects are mediated mainly by suppressing p38 mitogen-activated protein kinases, nuclear factor-kappa B, and nod-like receptor protein 3 signals. These effects are confirmed and supported by molecular docking. Clinical translational research is required to accelerate the bench-to-bedside transfer and determine whether galangin can be utilised as a safe, natural source of pharmaceutical anti-inflammatory medication for humans.

Pharmacological updates of nifuroxazide: Promising preclinical effects and the underlying molecular mechanisms.

Nifuroxazide (NFX) is a safe nitrofuran antibacterial drug used clinically to treat acute diarrhea and infectious traveler diarrhea or colitis. Recent studies revealed that NFX displays multiple pharmacological effects, including anticancer, antioxidant, and anti-inflammatory effects. NFX has potential roles in inhibiting thyroid, breast, lung, bladder, liver, and colon cancers and osteosarcoma, melanoma, and others mediated by suppressing STAT3 as well as ALDH1, MMP2, MMP9, Bcl2 and upregulating Bax. Moreover, it has promising effects against sepsis-induced organ injury, hepatic disorders, diabetic nephropathy, ulcerative colitis, and immune disorders. These promising effects appear to be mediated by suppressing STAT3 as well as NF-κB, TLR4, and ß-catenin expressions and effectively decreasing downstream cytokines TNF-α, IL-1ß, and IL-6. Our review summarizes the available studies on the molecular biological mechanisms of NFX in cancer and other diseases and it is recommended to translate the studies in experimental animals and cultured cells and repurpose NFX in various diseases for scientific evidence based on human studies.